EFFICIENT PRODUCTION OF ANTI-(HEPATITIS-B VIRUS) ANTIBODIES AND THEIRNEUTRALIZING ACTIVITY IN CHIMPANZEES

For industrial production of human monoclonal antibodies (hmAb) agains t hepatitis B virus surface antigen (HBsAg), we scaled-up a short-term perfusion culture in serum-free medium, which was chosen as the most suitable culture method, to a 50-1 fermenter equipped with a rotating shear filter. Using hydrophobic chromatography as the initial step of hmAb purification, the mAb HBW4, HBW6 and W471 were isolated in good q uality from the respective culture broths in yields of approximately 7 5%. Each of the three purified hmAb alone, and a cocktail of the three , protected chimpanzees against HB virus, when injected intravenously 3 h after viral challenge, as long as the serum antibody levels were s ignificant. A pharmacokinetic study using cynomolgus monkeys demonstra ted that the hmAb have a long plasma half-life and bioavailability of approximately 76% upon intramuscular injection in primates. Thus, anti -HBsAg hmAb produced by an industrial process are expected to be succe ssfully used in clinical fields.